VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
| Autor: | Carina Hellberg, Dietmar Vestweber, Heinz-Georg Belting, Makoto Hayashi, Sofie Mellberg, Markus Affolter, Gou Young Koh, Jeremy Adler, Simona Vertuani, Lars Holmgren, Xiujuan Li, Arindam Majumdar, Zuyue Sun, Anna Dimberg, Lena Claesson-Welsh, Sina Koch, Elisabetta Dejana, Gavin Thurston |
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| Rok vydání: | 2013 |
| Předmět: |
animal structures
Endothelium General Physics and Astronomy Biology Cell junction environment and public health Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell polarity medicine Animals Phosphorylation 030304 developmental biology 0303 health sciences Multidisciplinary Receptor-Like Protein Tyrosine Phosphatases Class 3 Cell Polarity Tyrosine phosphorylation General Chemistry Receptor TIE-2 Vascular Endothelial Growth Factor Receptor-2 Cell biology Vascular endothelial growth factor B Vascular endothelial growth factor Endothelial stem cell enzymes and coenzymes (carbohydrates) Intercellular Junctions medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis cardiovascular system Endothelium Vascular |
| Zdroj: | Nature communications Nature Communications |
| DOI: | 10.1038/ncomms2683 |
| Popis: | Vascular endothelial growth factor (VEGF) guides the path of new vessel sprouts by inducing VEGF receptor-2 activity in the sprout tip. In the stalk cells of the sprout, VEGF receptor-2 activity is downregulated. Here, we show that VEGF receptor-2 in stalk cells is dephosphorylated by the endothelium-specific vascular endothelial-phosphotyrosine phosphatase (VE-PTP). VE-PTP acts on VEGF receptor-2 located in endothelial junctions indirectly, via the Angiopoietin-1 receptor Tie2. VE-PTP inactivation in mouse embryoid bodies leads to excess VEGF receptor-2 activity in stalk cells, increased tyrosine phosphorylation of VE-cadherin and loss of cell polarity and lumen formation. Vessels in ve-ptp−/− teratomas also show increased VEGF receptor-2 activity and loss of endothelial polarization. Moreover, the zebrafish VE-PTP orthologue ptp-rb is essential for polarization and lumen formation in intersomitic vessels. We conclude that the role of Tie2 in maintenance of vascular quiescence involves VE-PTP-dependent dephosphorylation of VEGF receptor-2, and that VEGF receptor-2 activity regulates VE-cadherin tyrosine phosphorylation, endothelial cell polarity and lumen formation. Vascular endothelial growth factor is implicated in blood vessel development. In zebrafish, Hayashi et al. find that blood vessel development is dependent on the suppression of vascular endothelial growth factor by the phosphatase VE-PTP, which is recruited by activation of the angiopoietin receptor Tie2. |
| Databáze: | OpenAIRE |
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